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Food Chem Toxicol. 2018 Jan;111:19-26. doi: 10.1016/j.fct.2017.10.043. Epub 2017 Oct 27.

Pancreatic islet-autonomous effect of arsenic on insulin secretion through endoplasmic reticulum stress-autophagy pathway.

Author information

1
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
2
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China.
3
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lvshun South Road, Dalian 116044, PR China. Electronic address: sunxiance@dmu.edu.cn.

Abstract

Inorganic arsenic is a worldwide environmental pollutant. Arsenic's relationship with the incidence of diabetes arouses concerns on its etiological mechanism. In this study, the glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets of As2O3-treated mice was significantly lower than that of control mice. It indicated that the effect of As2O3-inhibited GSIS was pancreatic islet-autonomous. The level of phospho-PERK (p-PERK), a biomarker of endoplasmic reticulum (ER) stress, in pancreas of As2O3-treated mice was increased significantly. After treatment with NaAsO2, the p-PERK level in INS-1 rat pancreatic β- cells was increased correspondingly. After treatment with PERK inhibitor, the GSIS from isolated pancreatic islets of As2O3-treated mice was recovered. Arsenic induced autophagy in pancreatic islets, as evidenced by elevated LC3-II level and depressed P62 level in vivo and in vitro. In NaAsO2-treated INS-1 cells, the initiation of ER stress preceded the stimulation of autophagy, which was a key factor controlling pancreatic β cell function. Furthermore, knockdown of PERK attenuated NaAsO2-induced autophagy in INS-1 cells. These data indicated that arsenic impaired β cell function through ER stress-autophagy pathway. The present study will provide new mechanistic insights into arsenic-related diabetes.

KEYWORDS:

Arsenic; Autophagy; Endoplasmic reticulum stress; Insulin secretion; PERK

PMID:
29111283
DOI:
10.1016/j.fct.2017.10.043
[Indexed for MEDLINE]

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